Folic Acid Supplementation and the Association between Maternal Airborne Particulate Matter Exposure and Preterm Delivery: A National Birth Cohort Study in China

Background: Potential modification of the association between maternal particulate matter (PM) exposure and preterm delivery (PTD) by folic acid (FA) supplementation has not been studied.

Objective: We examined whether FA supplementation could reduce the risk of PTD associated with maternal exposure to PM in ambient air during pregnancy.

Method: In a cohort study covering 30 of the 31 provinces of mainland China in 2014, 1,229,556 primiparas of Han ethnicity were followed until labor. We collected information on their FA supplementation and pregnancy outcomes and estimated each participant's exposure to PM with diameters of $\le 10\mu m$ (${\mathrm{PM}}_{10}$), $2.5\mu m$ (${\mathrm{PM}}_{2.5}$), and $1\mu m$ (${\mathrm{PM}}_1$) using satellite remote-sensing based models. Cox proportional hazard regression models were used to examine interactions between FA supplementation and PM exposures, after controlling for individual characteristics.

Results: Participants who initiated FA $\ge 3\text{months}$ prior to pregnancy (38.1%) had a 23% [hazard ratio $\left(\text{HR}\right)=0.77$ (95% CI: 0.76, 0.78)] lower risk of PTD than women who did not use preconception FA. Participants with PM concentrations in the highest quartile had a higher risk of PTD [$\text{HR}=1.29$ (95% CI: 1.26, 1.32) for ${\mathrm{PM}}_1$, 1.52 (95% CI: 1.46, 1.58) for ${\mathrm{PM}}_{2.5}$, and 1.22 (95% CI: 1.17, 1.27) for ${\mathrm{PM}}_{10}$] than those with exposures in the lowest PM quartiles. Estimated associations with a $10\text{-}{\mu g/m}^3$ increase in ${\mathrm{PM}}_1$ and ${\mathrm{PM}}_{2.5}$ were significantly lower among women who initiated FA $\ge 3\text{months}$ prior to pregnancy [$\text{HR}=1.09$ (95% CI: 1.08, 1.10) for both exposures] than among women who did not use preconception FA [$\text{HR}=1.12$ (95% CI: 1.11, 1.13) for both exposures; $p_{\text{interaction}}<0.001$]. The corresponding association was also significantly lower for a $10{\text{-}\mu g/m}^3$ increase in ${\mathrm{PM}}_{10}$ [$\text{HR}=1.03$ (95% CI: 1.02, 1.03) for FA $\ge 3\text{months}$ before pregnancy vs. 1.04 (95% CI: 1.03, 1.04) for no preconception FA; $p_{\text{interaction}}<0.001$].

Conclusion: Our findings require confirmation in other populations, but they suggest that initiating FA supplementation $\ge 3\text{months}$ prior to pregnancy may lessen the risk of PTD associated with PM exposure during pregnancy among primiparas of Han ethnicity. https://doi.org/10.1289/EHP6386.